Abstract
Colorectal cancer is a malignant tumor arising from the inner lining of the colon or rectum and is the third most common cancer and the third leading cause of cancer-related deaths in the United States. Human epidermal growth factor receptor 2 (HER2) gene overexpressed or amplified colorectal cancer has shown treatment responses with HER2-directed therapies. We present a 78-year-old woman with metastatic colorectal cancer with a HER2 L726I mutation identified in tumor sequencing with amplification or overexpression of HER2. She had an excellent response to fam-trastuzumab deruxtecan. Our case is the first and most noteworthy case of a patient with metastatic colorectal cancer and a HER2 L726I mutation who achieved a remarkable clinical response to fam-trastuzumab deruxtecan.